Fractures and Low Bone Mineral Density Are Common in Adults With Cerebral Palsy

Commentary by Anne Trinh, MD and Mark Peterson, PhD, MS

Fractures and low bone mineral density (BMD) are relatively common among adults with cerebral palsy (CP), according to a retrospective cross-sectional study in the March issue of the TheJournal of Clinical Endocrinology and Metabolism. The study showed a link between hypogonadism and low BMD as well as reduced lean tissue mass in this population.

“Given adults with CP are living longer, bone and musculoskeletal health is an increasingly important issue,” explained lead author Anne Trinh, MD, Endocrinologist and Research Fellow at the Hudson Institute of Medical Research and Monash Health in Melbourne, Australia. “Osteoporosis and fractures are common in young adults with CP, particularly in those who are non-ambulatory,” Dr. Trinh said.

The study involved 45 adults with CP (mean age, 28.3 years) who underwent dual energy x-ray absorptiometry (DXA) aT a single hospital between 2005 and 2015.

Fracture History Found in More Than a Third of Patients
A total of 17 patients (38%) had a history of fragility fracture, with 53% of these fractures occurring in adulthood. The fracture sites in adulthood were vertebrae (n=4), ankle (n=3), ribs (n=2), and sacrum (n=1).

Low bone mineral density (ie, Z-score of ≤2.0) at the lumbar spine and femoral neck was found in 43% and 41% of the patients, respectively. In non-ambulatory patients, fracture risk was significantly associated with bone mineral content, areal BMD, and femoral neck Z-score (P<0.05). In fact, every one-unit decrease in femoral neck Z-score was associated with a 3.2-fold increased risk of fracture (P=0.044).

Functional status as assessed using the Gross Motor Function Classification System was the best predictor of Z-score at the lumbar spine and total hip (P=0.002) on stepwise linear regression.

Hypogonadism Linked to Reduced Bone Mineral Content and Lean Tissue Mass
Hypogonadism was found in 9 patients (20%). These patients were significantly shorter and weighed less than patients who were eugonadal (P=0.044 and P=0.013, respectively). In addition, patients with hypogonadism had significantly reduced lean tissue mass (25.2 kg vs 36.0 kg; P=0.040) and lumbar spine Z-score (-1.25 vs -3.06; P=0.045) compared with those who were eugonadal, after adjusting for gender.

Screening for Osteoporosis Should Be Considered for Adults With Cerebral Palsy
“Physicians caring for these adults should consider screening for osteoporosis with a DXA scan,” Dr. Trinh told EndocrineWeb. “If low bone mineral density (BMD) is confirmed, it is important to ensure that potential contributing factors to low BMD are not missed. This includes a screen for hypogonadism, as 20% of patients in this study had evidence of hypogonadism with associated detrimental changes in BMD and muscle.”

“Physicians also should consider performing lateral thoracolumbar x-rays in patients with low BMD, as vertebral fractures were identified in 4 out of 20 young adults who had a screening thoracolumbar x-ray,” Dr. Trinh said. “These fractures are not usually seen in young adults, and this finding warrants further research and confirmation in larger groups.”

Should All Patients With Cerebral Palsy Be Evaluated and Treated for Hypogonadism?
Dr. Trinh suggested that all adults with CP should be evaluated for hypogonadism “as this can have a devastating impact on their bone density if not identified in early adulthood.” She added that sex steroids also are important for optimal muscle function, especially in this population as many patients with CP already have decreased muscle mass.

“Young adults who are immobile and those who are fed by percutaneous endoscopic gastrostomy (PEG) tubes are most likely to have concurrent hypogonadism,” Dr. Trinh noted. “Treatment options should be discussed with patients and their carers. From our experience, hormone replacement is well tolerated.”

Are Osteoporosis Treatments Useful in Patients With Cerebral Palsy?
Dr. Trinh noted that there was a lack of knowledge regarding the efficacy of osteoporosis medications in adults with CP. “In studies of children with CP, there is some evidence that intravenous bisphosphonates and vibration platforms can increase BMD,” Dr. Trinh said. “From our data, it appears that muscle mass is important for optimal bone mineral density, but only if patients are eugonadal. Thus, screening and treating hypogonadism prior to exercise interventions is paramount,” she said.

Commentary

Although by definition, cerebral palsy (CP) is a “non-progressive” condition, secondary factors such as muscle weakness, sarcopenia, obesity, and habitual sedentary behaviors may increase the severity of functional impairment throughout adulthood. Unfortunately, over one-third of ambulatory children with CP are at risk for losing the ability to walk by early adulthood, which further increases the likelihood of frailty, obesity-related cardiometabolic disease, and early mortality. Indeed, we have recently shown that individuals with CP have increased intermuscular and visceral adipose tissue,1 and higher odds of developing chronic conditions such as diabetes, stroke, asthma, hypertension, and other heart conditions.2

The recent study by Trinh et al3 extends our work to demonstrate that adults with CP also have low bone mineral density and are at elevated risk for fractures. Moreover, their study indicates, for the first time, that adults with CP are at substantially greater risk for hypogonadism (particularly among more severely impaired individuals and/or individuals who were tube fed), thereby placing them at even higher risk of low musculoskeletal density and strength.

Thus, there is a critical need for clinical strategies that can address both early screening efforts among adolescents and young adults with CP, but also to devise strategies such as tailored physical activity and healthy nutrition interventions to bolster preservation of neuromuscular function, cardiometabolic health, and musculoskeletal integrity in this population.